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Background: Venlafaxine hydrochloride (VFH) is an antidepressant drug with poor bioavailability due to extensive first-pass metabolism. Objective: In the present study, oro-dispersible VFH tablets were prepared using an effervescent method to enhance patient compliance using a design of experiment (DoE) approach. Methods: A two-factor, three-level 32 full factorial design was applied to investigate the combined effect of two formulation variables: the amount of treated agar and effervescent material (mixture of sodium bicarbonate, citric acid and tartaric acid) on disintegration time and %drug release (Critical quality attributes). Treated agar (12-18%w/w) was used as a disintegrant, and a mixture of sodium bicarbonate, citric acid and tartaric acid (12-16%w/w) was used as effervescent material along with directly compressible excipients to enhance mouth feel. The association between the factors and responses was established by plotting response surfaces and contour plots. A 3D surface plot was used further to evaluate the responses to the factors. Prepared tablets were evaluated for wetting time, hardness, friability, thickness, drug content uniformity, and disintegration time. In vitro, drug release studies and stability studies were also performed. Results: The tablet formulation containing 17.5% w/w treated agar and 16%w/w mixture of sodium bicarbonate, citric acid and tartaric acid was found to be a promising formulation with a disintegration time of 27 seconds and in vitro drug release of 97.38% (in phosphate buffer of pH 6.8). Conclusion: The use of effervescent material was found to be useful for taste masking as well as patient compliance.

This study introduces a novel chemiluminescence (CL) approach utilizing FeS2 nanosheets (NSs) catalyzed luminol–O2 CL reaction for the measurement of three pharmaceuticals, namely venlafaxine hydrochloride (VFX), imipramine hydrochloride (IPM), and cefazolin sodium (CEF). The CL method involved the phenomenon of quenching induced by the pharmaceuticals in the CL reaction. To achieve the most quenching efficacy of the pharmaceuticals in the CL reaction, the concentrations of reactants comprising luminol, NaOH, and FeS2 NSs were optimized accordingly. The calibration curves demonstrated exceptional linearity within the concentration range spanning from 4.00 × 10−7 to 1.00 × 10−3 mol L−1, 1.00 × 10−7 to 1.00 × 10−4 mol L−1, and 4.00 × 10−6 to 2.00 × 10−4 mol L−1 with detection limits (3σ) of 3.54 × 10−7, 1.08 × 10−8, and 2.63 × 10−6 mol L−1 for VFX, IPM, and CEF, respectively. This study synthesized FeS2 NSs using a facile hydrothermal approach, and then the synthesized FeS2 NSs were subjected to a comprehensive characterization using a range of spectroscopic methods. The proposed CL method was effective in measuring the aforementioned pharmaceuticals in pharmaceutical formulations as well as different water samples. The mechanism of the CL system has been elucidated. [ABSTRACT FROM AUTHOR]

Venlafaxine, primarily available in dosage in Venlafaxine hydrochloride (VEN.HCl) form, is a discriminating serotonin and norepinephrine reuptake inhibitor (SNRI) anti-depressant drug. The 4-methoxybenzyl chloride (4-MBC) is a genotoxic impurity present in VEN.HCl. A reverse-phase high-performance liquid chromatography (RP-HPLC) method is developed for the determination of 4-MBC content this method is validated employing ICH (International Council on Harmonisation) guidelines. During the method development, Purospher STAR end-capped (250mmx4.0mm), 5µm HPLC column, and gradient profile for mobile phase with constant 1.0 mL/min flow rate are used. Mobile phase A is a buffer of pH 8.5 containing 0.1% v/v of liquid ammonia in water with adjusted pH using 10% orthophosphoric acid, whereas mobile phase B is acetonitrile. The injection volume, column oven temperature, and autosampler temperature were 50 µL, 55°C, and 5°C, respectively. The data is acquired at 225 nm wavelength. The method yields a well-separated peak of 4-MBC from Venlafaxine and its impurities. This method is linear in the range of LOQ to 150% level of specification concentration of impurity and the observed correlation coefficient is 0.999. The repeatability and intermediate precision are evaluated and the respective values of %RSD for 4-MBC content are 0.43 and 0.93. Robustness studies show insignificant change for the system suitability criteria like %RSD, theoretical plates, and tailing factor, their values being well within the acceptance limit. The new method for the quantification of genotoxic impurity 4-MBC is precise, sensitive, rugged, and accurate; it also qualifies all the criteria of stability, linearity, and robustness. [ABSTRACT FROM AUTHOR]

Objective: Vestibular migraine is in the process of recognition as an individual clinical entity. At present, no guidelines exist for its management. This study aimed to conduct a systematic review and meta-analysis to determine the effectiveness of available prophylactic medication. Method: A literature search was performed using PubMed, Ovid and Embase databases. Qualitative and quantitative analysis were performed as well as risk of bias analysis. Meta-analysis for the mean differences for pre- and post-treatment impact based on Dizziness Handicap Inventory and Vertigo Symptom Scale were performed. Proportionate transformation meta-analysis for the successful event rate based on complete symptoms control was explored. Results: Thirteen publications were identified: 3 were randomised, controlled trials and 10 were non-randomised, controlled trials. Propranolol and venlafaxine improved the Vertigo Symptom Scale score by −13.31 points and −4.16 points, respectively, and the Dizziness Handicap Inventory score by −32.24 and −21.24, respectively. Only propranolol achieved statistically significant impact with 60 per cent of patients achieving complete symptom control. Conclusion: Propranolol should be offered as the first-line treatment for vestibular migraine followed by venlafaxine. Amitriptyline, flunarizine and cinnarizine showed a trend for symptom improvement, but this was not statistically significant. [ABSTRACT FROM AUTHOR]

BACKGROUND: One of the key mechanisms underlying OSA is reduced pharyngeal muscle tone during sleep. Data suggest that pharmacologic augmentation of central serotonergic/adrenergic tone increases pharyngeal muscle tone. RESEARCH QUESTION: We hypothesized that venlafaxine, a serotonin-norepinephrine reuptake inhibitor, would improve OSA severity. STUDY DESIGN AND METHODS: In this mechanistic, randomized, double-blind, placebo-controlled crossover trial, 20 patients with OSA underwent two overnight polysomnograms ≥ 4 days apart, receiving either 50 mg of immediate-release venlafaxine or placebo before bedtime. Primary outcomes were the apnea-hypopnea index (AHI) and peripheral oxygen saturation (Spo2) nadir, and secondary outcomes included sleep parameters and pathophysiologic traits with a view toward understanding the impact of venlafaxine on mechanisms underlying OSA. RESULTS: Overall, there was no significant difference between venlafaxine and placebo regarding AHI (mean reduction, -5.6 events/h [95% CI, -12.0 to 0.9]; P = .09) or Spo2 nadir (median increase, +1.0% [-0.5 to 5]; P = .11). Venlafaxine reduced total sleep time, sleep efficiency, and rapid eye movement (REM) sleep, while increasing non-REM stage 1 sleep (Pall < .05). On the basis of exploratory post hoc analyses venlafaxine decreased (improved) the ventilatory response to arousal (-30%; P = .049) and lowered (worsened) the predicted arousal threshold (-13%; [P = .02]; ie, more arousable), with no effects on other pathophysiologic traits (Pall ≥ .3). Post hoc analyses further suggested effect modification by arousal threshold (P = .002): AHI improved by 19% in patients with a high arousal threshold (-10.9 events/h [-3.9 to -17.9]) but tended to increase in patients with a low arousal threshold (+7 events/h [-2.0 to 16]). Other predictors of response were elevated AHI and less collapsible upper airway anatomy at baseline (|r| > 0.5, P ≤ .02). INTERPRETATION: In unselected patients, venlafaxine simultaneously worsened and improved various pathophysiologic traits, resulting in a zero net effect. Careful patient selection based on pathophysiologic traits, or combination therapy with drugs countering its alerting effects, may produce a more robust response. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT02714400; URL: www.clinicaltrials.gov.

Objective:The purpose of this study was to examine the influence of comorbid anxiety symptoms on antidepressant treatment remission in older adults with major depressive disorder (MDD).Method:In this multisite clinical trial, 468 older adults aged 60 years or older with MDD received open-label protocolized treatment with venlafaxine extended release (ER) titrated to a maximum of 300 mg daily. At baseline, anxiety was assessed with the Anxiety Sensitivity Index, the Brief Symptom Inventory (BSI) anxiety subscale, and the Penn State Worry Questionnaire. To measure treatment response, depressive symptoms and suicidality were assessed every 1-2 weeks with the Montgomery-Asberg Depression Rating Scale and the 19-item Scale for Suicide Ideation; anxiety was assessed with the BSI. Logistic regression and survival analysis were used to evaluate whether anxiety symptoms predicted depression remission. We also examined the relationships between anxiety scores and suicidality at baseline.Results:Baseline anxiety symptoms did not predict remission or time to remission of depressive symptoms. Depressive, worry, and panic symptoms decreased in parallel in patients with high anxiety. Anxiety symptoms were associated with the severity of depression and with suicidality.Conclusion:In older adults with MDD, comorbid anxiety symptoms are associated with symptom severity but do not affect antidepressant remission or time to remission.